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Announcements • Today – Signaling pathways and 2nd messengers – Pituitary gland – Course evaluations Two types of hormones • Lipid Soluble – Steroid hormones (estrogen, testosterone) – Thyroid hormones • Lipid Insoluble – Peptides and Proteins (insulin) – Catecholamines (adrenalin) Two types of hormones 1. Lipid-soluble Carrier molecule Hormone molecule Cytoplasmic receptor Nuclear receptor Transcription & Translation long lasting effects Nucleus Two types of hormones 2. Lipid-insoluble Hormone molecule Plasma membrane receptor Second Messenger Effector Protein Cellular effects Signal Transduction Signal Reception, Transduction Amplification Second Messengers Regulators Specific Effectors Cellular Response Types of Second Messengers • Cyclic nucleotides – cAMP, cGMP • Inositol phospholipid – Inositol 1,4,5 triphosphate (IP3) – 1,2-diacylglycerol (DAG) • Calcium ions (Ca++) cAMP / Protein Kinase A Pathway Ri Rs Adenylate Cyclase Gs Gi stimulates ATP cAMP Protein Kinase A Ion Channels Membrane Pumps Metabolic Enzymes inhibits cAMP / Protein Kinase A Pathway Ri Rs Adenylate Cyclase Gs ATP Gi cAMP Regulatory subunit Protein Kinase A Catalytic subunit Effects Inositol Phospholipid Pathway Phospholipase C PIP2 DAG PS Protein Kinase C G-protein IP3 Ca++ Cellular Response Intracellular Ca++ stores Other Ca++ Dependent processes 1. Receptor / G-protein activate phospholipase C 2. PLC catalyzes PIP2 IP3 and DAG 3. IP3 release of Ca++ from intracellular stores (ER) 4. DAG (together with Ca++ and PS) activate Protein Kinase C Phosphatidylserine Calcium as second messenger Ca++ Guanylate kinase GTP Ca++ Intracellular Ca++ stores cGMP Neurotransmitter release Muscle contraction Protein Kinase C Cam Kinase II Protein Kinase G Calcium / Calmodulin Adenylate cyclase Metabolic Enzymes Pituitary gland • Master gland – Secretes 9 hormones that control other glands • 2 distinct parts – Anterior pituitary (adenohypophysis) – Posterior pituitary (neurohypophysis) • Both parts controlled by neurosecretory cells of the hypothalamus (part of the brain!) Neural Inputs Hypothalamus Portal Blood Vessels Fig 9-15 Anterior Pituitary -glandular tissue Posterior Pituitary Anterior Pituitary Hypothalamus Hormone 1 Portal blood vessels Hormone 1 Target Tissue Anterior Pituitary Hormone 2 Posterior Pituitary Hypothalamus Hormone 1 Portal blood vessels Target Tissue Posterior Pituitary • Neurosecretory neurons Anterior Pituitary – Secrete hormones into portal blood vessels – Regulate secretion of other hormones from anterior pituitary • Neurosecretory neurons Posterior Pituitary – Secrete hormones directly into capillaries Anterior Pituitary • 2 hormone system • 1st hormone stimulates or inhibits release of other hormones from anterior pituitary • 2nd hormone has effect on target tissue Examples: • 1st hormone • 2nd hormone – Corticotropin-releasing hormone (CRH) – Adrenocorticotropin hormone (ACTH) – Thyroid hormone releasing hormone (TRH) – Thyroid stimulating hormone (TSH) – Prolactin-inhibiting hormone (PIH) – Prolactin Control of Anterior Pituitary Hypothalmic Neurosecretory cells Negative feedback Releasing and release-inhibiting hormones Anterior pituitary gland Growth hormone Non-endocrine Tissue Metabolic response ACTH Thyroid Stimulating Hormone Other Endocrine Tissue Posterior Pituitary • • Neurosecretory cells secrete hormones directly onto capillaries Only 2 hormones: 1. Antidiuretic hormone (ADH, also called vasopressin) • Water retention by the kidney 2. Oxytocin • • Uterine contractions during childbirth Milk ejection during breast feeding The Adrenal Glands • An example of Pituitary control over other endocrine tissue • One gland attached to the top of each kidney Adrenal Medulla Adrenal Cortex Fig 9-32 Kidney Adrenal Cortex • Steroid hormones – Aldosterone – Cortisol – Small amounts of testosterone, progesterone Adrenal Medulla • Catecholamine – Epinipherine (adrenalin) – Norepinipherine (noradrenalin) Control of Adrenal Cortex Stress, circadian rhythm and other neural input Hypothalamic neurons Corticotropin releasing hormone (CRH) Anterior Pituitary Adrenocorticotropic hormone (ACTH) Adrenal cortex Release of steroid hormones Adrenal Cortical Steroids • Mineralocorticoids – eg. aldosterone – Controls ion transport in the kidney function – Regulates expression of a Na channel – Important for water reabsorption • Glucocorticoids – eg. cortisol – Important for metabolism esp. glucose – Activate enzymes (in liver) that increase glucose production – blood glucose Adrenal Medulla • Catecholamines stored in large vesicles within chromaffin cells of the adrenal medulla • Chromaffin cells innervated by neurons of the sympathetic nervous system • ‘Fight or flight’ response Sympathetic nerve terminal Acetycholine synapse Ca++ Adrenal medulla Catecholamine containing vesicles Chromaffin cell Blood vessel • Ach depolarizes chromaffin cell by activating nicotinic Ach receptors • Opens voltage-gated Ca++ channels • Ca++ causes fusion of vesicles • Release of catecholamine into blood stream • Catecholamines released by adrenal medulla: – epinipherine 80% – norepiniphrine 20% – Also neurotransmitter • Norepinephrine primary SNS Effects of catecholamines depend upon receptor type • Activate adrenoreceptors – Two types: and 1 Phospholipase C IP3 & DAG 2 1 2 Adenylate cyclase cAMP Potential effects of catecholamine receptor activation • Heart – , mediated - contraction, HR • Smooth Muscle (Blood vessels and lungs) – contraction – relaxation • Metabolism – - glycogenolysis glucose • Neural – - K+ channel conductance Some clinical stuff • adrenoreceptor agonists used to treat asthma • blockers used to treat high blood pressure Summary • Pituitary gland – Hypothalamic control – Anterior – 2 hormone system – Posterior – direct hormone release into blood stream • Adrenal gland – Cortex – steroid hormones – Medulla - catecholamines Blood Glucose Regulation • Endocrine pancreas – Only 2% of entire pancreas, – the rest produces digestive enzymes (exocrine) – Islets of Langerhans • Insulin ( cells) • Glucagon ( cells) • Somatostatin ( cells) • Diabetes – 2 million Canadians – $9 billion per year health care costs – Insulin isolated by Banting & Best 1922, U of T Dept of Physiology (1923 Nobel Prize) • Type 1 – No or very little insulin produced • Type 2 – Reduced cellular response to insulin • Consequences – – – – Death Blindness Kidney disease Limb amputation Hormonal control of blood glucose In the GI tract, 80% of all carbohydrate is digested to glucose Basically: Glucose Used for ATP production Glycogen Used for glucose storage Insulin • Stimulus for secretion is high blood glucose • Secreted by cells • Leads to glucose uptake and storage in liver, muscle and fat tissue. • Effect is to blood glucose • Danger of Diabetes is hyperglycemia Insulin Effects on Muscle and Fat Tissue • Insulin initiates transfer of glucose transporters to cell membrane • blood glucose • production of glycogen Effects in Muscle & Fat Glycogen synthesis Glucose transporter glucose SNARE dependent transport Glucose transporter Insulin storage vesicle In the Liver • insulin stimulates the synthesis of an enzyme (glucokinase) • Required to ‘trap’ glucose in the cell • initiates glycogen production Effects in Liver GLUT2 Glycogen synthesis Glucose transporter glucose X glucose Glucose 6-phosphate glucokinase ‘trapped’ Other hormones • Glucagon – Secretion stimulated by low blood glucose – Activates enzymes for gluconeogenesis and glycogenolysis – Leads to blood glucose levels • Somatostatin – Regulates secretion of insulin and glucagon Glucose Regulation Summary • Endocrine pancreas • Secretion of several hormones important for blood glucose regulation • Insulin glucose uptake and storage – Different effects on liver and muscle & fat • Glucagon glucose production • Today – Finish blood glucose – Some words about the final – Sample questions Effects in Muscle & Fat GLUT4 Glycogen synthesis Glucose transporter glucose SNARE dependent transport Glucose transporter Insulin storage vesicle Insulin Effects on Muscle and Fat Tissue • Insulin initiates transfer of glucose transporters to cell membrane • blood glucose • production of glycogen In the Liver • insulin stimulates the synthesis of an enzyme (glucokinase) • Required to ‘trap’ glucose in the cell • initiates glycogen production Effects in Liver GLUT2 Glycogen synthesis Glucose transporter glucose X glucose Glucose 6-phosphate glucokinase ‘trapped’ Other hormones • Glucagon – Secretion stimulated by low blood glucose – Activates enzymes for gluconeogenesis and glycogenolysis – Leads to blood glucose levels • Somatostatin – Regulates secretion of insulin and glucagon Glucose Regulation Summary • Endocrine pancreas & cell type • Secretion of several hormones important for blood glucose regulation • Insulin glucose uptake and storage – Different effects on liver and muscle & fat • Glucagon glucose production